Structural determinants of subunit -subunit interactions and subcellular localization of the calcium /calmodulin -dependent protein kinase II

The multifunctional Ca$\sp{2+}$/calmodulin-dependent protein kinase II (CaM kinase) is a Ser/Thr directed protein kinase that participates in diverse Ca$\sp{2+}$ signaling pathways in neurons. The function of CaM kinase depends upon the ability of subunits to form oligomers and to interact with other proteins. Oligomerization is required for autophosphorylation which produces significant functional changes that include Ca$\sp{2+}$/calmodulin-independent activity and calmodulin trapping. Associations with other proteins localize CaM kinase to specific substrates and effectors which serves to optimize the efficiency and speed of signal transduction. In this thesis, we investigate the interactions that underlie the appropriate positioning of CaM kinase activity in cells. We demonstrate that the subcellular distribution of CaM kinase is dynamic in hippocampal slices exposed to anoxic/aglycemic insults and to high K$\sp{+}$-induced depolarization. We determine the localization of CaM kinase domains expressed in neurons and PC-12 cells and find that the C-terminal domain of the $\alpha$ subunit is necessary for localization to dendrites. Moreover, monomeric forms of the enzyme gain access to the nucleus. Attempts made to identify novel CaM kinase binding proteins using the yeast two-hybrid system resulted in the isolation of hundreds of positive clones. Those that have been sequenced are identical to CaM kinase isoforms. Finally, we report the discovery of specific regions within the C-terminal domain that are necessary and sufficient for subunit-subunit interactions. Differences between the $\alpha$ and $\beta$ isoforms were discovered that indicate unique structural requirements for oligomerization. A model for how CaM kinase subunits interact to form holoenzymes and how structural heterogeneity might influence CaM kinase function is presented. ^

Boron isotopes, pH and pCO2 calculation for one Fiji coral specimen Porites (1898-1998), 2012

delta11B results and deduced pH, pCO2 and omega values obtained for a tropical coral specimen Porites collected in 1998 at Yasawa (16°48'S- 177°27'E) on the western side of the Fiji archipelago, location in the north western part of the Pacific Warm Pool. Such Porites specimen grew during the XXth century (1898-1998). Boron isotopes results allowed the reconstruction of surface ocean acidification in the vincinity of Fiji Islands with strong interdecadal influence of the ENSO at regional scale. pHT calculation parameters (Hönisch et al., 2007): a=0 PER MIL; alpha=0.9804; delta11B=39.5 PER MIL; salinity=35.02; pKB from Dickson (1990). pCO2 and omega calculation parameters: TA= 2350 µM; Ca= 10.2 mM; Dickson et al.(2007); Mucci 1983.

Ion concentration and deduced chemical compounds of the GRIP and Dome Fuji ice cores, Greenland and Antarctica

We have proposed a method of deducing the chemical compounds found in deep polar ice cores by analyzing the balance between six major ions (Cl-, NO3-, SO4**2-, Na+, Mg2+, and Ca2+). The method is demonstrated for the Holocene and last glacial maximum regions of the Dome Fuji and GRIP ice cores. The dominant compounds depend only on the ion balance and the sequence of chemical reactions. In priority order, the principle salts are calcium sulfate, other sulfates, nitrate, chloride, and carbonate. The chemical abundances deduced by this method agree well with the results of Raman spectroscopy on individual salt inclusions. The abundances in the ice cores are shown to reflect differences in climatic periods (the acidic environment of the Holocene versus the reductive environment of the last glacial maximum) and regional conditions (the marine environment of Antarctica versus the continental environment of Greenland).

High-resolution multi-proxy record of the last interglacial period from Lake Van, eastern Anatolian high plateau, Turkey

A high-resolution multi-proxy record from Lake Van, eastern Anatolia, derived from a lacustrine sequence cored at the 357 m deep Ahlat Ridge (AR), allows a comprehensive view of paleoclimate and environmental history in the continental Near East during the last interglacial (LI). We combined paleovegetation (pollen), stable oxygen isotope (d18Obulk) and XRF data from the same sedimentary sequence, showing distinct variations during the period from 135 to 110 ka ago leading into and out of full interglacial conditions. The last interglacial plateau, as defined by the presence of thermophilous steppe-forest communities, lasted ca. 13.5 ka, from ~129.1-115.6 ka BP. The detailed palynological sequence at Lake Van documents a vegetation succession with several climatic phases: (I) the Pistacia zone (ca. 131.2-129.1 ka BP) indicates summer dryness and mild winter conditions during the initial warming, (II) the Quercus-Ulmus zone (ca. 129.1-127.2 ka BP) occurred during warm and humid climate conditions with enhanced evaporation, (III) the Carpinus zone (ca. 127.2-124.1 ka BP) suggest increasingly cooler and wetter conditions, and (IV) the expansion of Pinus at ~124.1 ka BP marks the onset of a colder/drier environment that extended into the interval of global ice growth. Pollen data suggest migration of thermophilous trees from refugial areas at the beginning of the last interglacial. Analogous to the current interglacial, the migration documents a time lag between the onset of climatic amelioration and the establishment of an oak steppe-forest, spanning 2.1 ka. Hence, the major difference between the last interglacial compared to the current interglacial (Holocene) is the abundance of Pinus as well as the decrease of deciduous broad-leaved trees, indicating higher continentality during the last interglacial. Finally, our results demonstrate intra-interglacial variability in the low mid-latitudes and suggest a close connection with the high-frequency climate variability recorded in Greenland ice cores.

Palynology on sediment profile Tso Kar in Ladakh

Palynological investigation of a 410 cm long core section from Tso Kar (33°10'N, 78°E, 4527 m a.s.l.), an alpine lake situated in the arid Ladakh area of NW India at the limit of the present-day Indian summer monsoon, was performed in order to reconstruct post-glacial regional vegetation and climate dynamics. The area was covered with alpine desert vegetation from ca. 15.2 to 14 kyr BP (1 kyr=1000 cal. years), reflecting dry and cold conditions. High influx values of long-distance transported Pinus sylvestris type pollen suggest prevailing air flow from the west and northwest. The spread of alpine meadow communities and local aquatic vegetation is a weak sign of climate amelioration after ca. 14 kyr BP. Pollen data (e.g. influx values of Pinus roxburghii type and Quercus) suggest that this was due to a strengthening of the summer monsoon and the reduced activity of westerly winds. The further spread of Artemisia and species-rich meadows occurred in response to improved moisture conditions between ca. 12.9 and 12.5 kyr BP. The subsequent change towards drier desert-steppe vegetation likely indicates more frequent westerly disturbances and associated snowfalls, which favoured the persistence of alpine meadows on edaphically moist sites. The spread of Chenopodiaceae-dominated vegetation associated with an extremely weak monsoon occurred at ca. 12.2-11.8 kyr BP during the Younger Dryas interstadial. A major increase in humidity is inferred from the development of Artemisia-dominated steppe and wet alpine meadows with Gentianaceae after the late glacial/early Holocene transition in response to the strengthening of the summer monsoon. Monsoonal influence reached maximum activity in the Tso Kar region between ca. 10.9 and 9.2 kyr BP. The subsequent development of the alpine meadow, steppe and desert-steppe vegetation points to a moderate reduction in the moisture supply, which can be linked to the weaker summer monsoon and the accompanying enhancement of the winter westerly flow from ca. 9.2 to 4.8 kyr BP. The highest water levels of Tso Kar around 8 kyr BP probably reflect combined effect of both monsoonal and westerly influence in the region. An abrupt shift towards aridity in the Tso Kar region occurred after ca. 4.8 kyr BP, as evidenced by an expansion of Chenopodiaceae-dominated desert-steppe. Low pollen influx values registered ca. 2.8-1.3 kyr BP suggest scarce vegetation cover and unfavourable growing conditions likely associated with a further weakening of the Indian Monsoon.

High-resolution sedimentological and paleontological record of ODP Site 167-1019

Holocene and latest Pleistocene oceanographic conditions and the coastal climate of northern California have varied greatly, based upon high-resolution studies (ca. every 100 years) of diatoms, alkenones, pollen, CaCO3%, and total organic carbon at Ocean Drilling Program (ODP) Site 1019 (41.682°N, 124.930°W, 980 m water depth). Marine climate proxies (alkenone sea surface temperatures [SSTs] and CaCO3%) behaved remarkably like the Greenland Ice Sheet Project (GISP)-2 oxygen isotope record during the Bølling-Allerod, Younger Dryas (YD), and early part of the Holocene. During the YD, alkenone SSTs decreased by >3°C below mean Bølling-Allerod and Holocene SSTs. The early Holocene (ca. 11.6 to 8.2 ka) was a time of generally warm conditions and moderate CaCO3 content (generally >4%). The middle part of the Holocene (ca. 8.2 to 3.2 ka) was marked by alkenone SSTs that were consistently 1-2°C cooler than either the earlier or later parts of the Holocene, by greatly reduced numbers of the gyre-diatom Pseudoeunotia doliolus (<10%), and by a permanent drop in CaCO3% to <3%. Starting at ca. 5.2 ka, coastal redwood and alder began a steady rise, arguing for increasing effective moisture and the development of the north coast temperate rain forest. At ca. 3.2 ka, a permanent ca. 1°C increase in alkenone SST and a threefold increase in P. doliolus signaled a warming of fall and winter SSTs. Intensified (higher amplitude and more frequent) cycles of pine pollen alternating with increased alder and redwood pollen are evidence that rapid changes in effective moisture and seasonal temperature (enhanced El Niño-Southern Oscillation [ENSO] cycles) have characterized the Site 1019 record since about 3.5 ka.

Benthic foraminiferal biofacies and stable isotopic record of St. Stephens Quarry, Alabama

We integrate upper Eocene-lower Oligocene lithostratigraphic, magnetostratigraphic, biostratigraphic, stable isotopic, benthic foraminiferal faunal, downhole log, and sequence stratigraphic studies from the Alabama St. Stephens Quarry (SSQ) core hole, linking global ice volume, sea level, and temperature changes through the greenhouse to icehouse transition of the Cenozoic. We show that the SSQ succession is dissected by hiatuses associated with sequence boundaries. Three previously reported sequence boundaries are well dated here: North Twistwood Creek-Cocoa (35.4-35.9 Ma), Mint Spring-Red Bluff (33.0 Ma), and Bucatunna-Chickasawhay (the mid-Oligocene fall, ca. 30.2 Ma). In addition, we document three previously undetected or controversial sequences: mid-Pachuta (33.9-35.0 Ma), Shubuta-Bumpnose (lowermost Oligocene, ca. 33.6 Ma), and Byram-Glendon (30.5-31.7 Ma). An ~0.9 per mil d18O increase in the SSQ core hole is correlated to the global earliest Oligocene (Oi1) event using magnetobiostratigraphy; this increase is associated with the Shubuta-Bumpnose contact, an erosional surface, and a biofacies shift in the core hole, providing a first-order correlation between ice growth and a sequence boundary that indicates a sea-level fall. The d18O increase is associated with a eustatic fall of ~55 m, indicating that ~0.4 per mil of the increase at Oi1 time was due to temperature. Maximum d18O values of Oi1 occur above the sequence boundary, requiring that deposition resumed during the lowest eustatic lowstand. A precursor d18O increase of 0.5 per mil (33.8 Ma, midchron C13r) at SSQ correlates with a 0.5 per mil increase in the deep Pacific Ocean; the lack of evidence for a sea-level change with the precursor suggests that this was primarily a cooling event, not an ice-volume event. Eocene-Oligocene shelf water temperatures of ~17-19 °C at SSQ are similar to modern values for 100 m water depth in this region. Our study establishes the relationships among ice volume, d18O, and sequences: a latest Eocene cooling event was followed by an earliest Oligocene ice volume and cooling event that lowered sea level and formed a sequence boundary during the early stages of eustatic fall.

Mineral composition and 40Ar-39Ar data of samples from Garnet Point, Aurora Peak, Correll Nunatak, Penguin Point and Horn Bluffs, East Antarctica

George V Land (Antarctica) includes the boundary between Late Archean-Paleoproterozoic metamorphic terrains of the East Antarctic craton and the intrusive and metasedimentary rocks of the Early Paleozoic Ross-Delamerian Orogen. This therefore represents a key region for understanding the tectono-metamorphic evolution of the East Antarctic Craton and the Ross Orogen and for defining their structural relationship in East Antarctica, with potential implications for Gondwana reconstructions. In the East Antarctic Craton the outcrops closest to the Ross orogenic belt form the Mertz Shear Zone, a prominent ductile shear zone up to 5 km wide. Its deformation fabric includes a series of progressive, overprinting shear structures developed under different metamorphic conditions: from an early medium-P granulite-facies metamorphism, through amphibolite-facies to late greenschist-facies conditions. 40Ar-39Ar laserprobe data on biotite in mylonitic rocks from the Mertz Shear Zone indicate that the minimum age for ductile deformation under greenschist-facies conditions is 1502 ± 9 Ma and reveal no evidence of reactivation processes linked to the Ross Orogeny. 40Ar-39Ar laserprobe data on amphibole, although plagued by excess argon, suggest the presence of a ~1.7 Ga old phase of regional-scale retrogression under amphibolite-facies conditions. Results support the correlation between the East Antarctic Craton in the Mertz Glacier area and the Sleaford Complex of the Gawler Craton in southern Australia, and suggest that the Mertz Shear Zone may be considered a correlative of the Kalinjala Shear Zone. An erratic immature metasandstone collected east of Ninnis Glacier (~180 km east of the Mertz Glacier) and petrographically similar to metasedimentary rocks enclosed as xenoliths in Cambro-Ordovician granites cropping out along the western side of Ninnis Glacier, yielded detrital white-mica 40Ar-39Ar ages from ~530 to 640 Ma and a minimum age of 518 ± 5 Ma. This pattern compares remarkably well with those previously obtained for the Kanmantoo Group from the Adelaide Rift Complex of southern Australia, thereby suggesting that the segment of the Ross Orogen exposed east of the Mertz Glacier may represent a continuation of the eastern part of the Delamerian Orogen.

Relative abundances of twenty-eight dominant benthic foraminifera species of DSDP Hole 23-219 (Table 1s)

Tropical climate is variable on astronomical time scale, driving changes in surface and deep-sea fauna during the Pliocene-Pleistocene. To understand these changes in the tropical Indian Ocean over the past 2.36 Myr, we quantitatively analyzed deep-sea benthic foraminifera and selected planktic foraminifera from >125 µm size fraction from Deep Sea Drilling Project Site 219. The data from Site 219 was combined with published foraminiferal and isotope data from Site 214, eastern Indian Ocean to determine the nature of changes. Factor and cluster analyses of the 28 highest-ranked species distinguished four biofacies, characterizing distinct deep-sea environmental settings. These biofacies have been named after their most dominant species such as Stilostomella lepidula-Pleurostomella alternans (Sl-Pa), Nuttallides umbonifer-Globocassidulina subglobosa (Nu-Gs), Oridorsalis umbonatus-Gavelinopsis lobatulus (Ou-Gl) and Epistominella exigua-Uvigerina hispido-costata (Ee-Uh) biofacies. Biofacies Sl-Pa ranges from ~2.36 to 0.55 Myr, biofacies Nu-Gs ranges from ~1.9 to 0.65 Myr, biofacies Ou-Gl ranges from ~1 to 0.35 Myr and biofacies Ee-Uh ranges from 1.1 to 0.25 Myr. The proxy record indicates fluctuating tropical environmental conditions such as oxygenation, surface productivity and organic food supply. These changes appear to have been driven by changes in monsoonal wind intensity related to glacial-interglacial cycles. A shift at ~1.2-0.9 Myr is observed in both the faunal and isotope records at Site 219, indicating a major increase in monsoon-induced productivity. This coincides with increased amplitude of glacial cycles, which appear to have influenced low latitude monsoonal climate as well as deep-sea conditions in the tropical Indian Ocean.

Radiocarbon ages of bottom sediments and sedimentation rates in depressions of the Red Sea rift zone

Sedimentation rates (SR) for metalliferous and ore sediments containing ore material in 15 depressions of the Red Sea rift zone are discussed. SR for normal sediments was ca. 3.2 cm/ka in the second half of Holocene, 14.3 cm/ka yrs in the first half of Holocene, and 21.3 cm/ka in Late Würmian. Accumulation of metalliferous and ore sediments requires considerable accumulation of hydrothermal matter. Ore sediments have been found primarily in the Atlantis II and Chain Deeps; average sedimentation rate in these depressions is 90.0 cm/ka. In other depressions geothermal activity during considered time intervals was lower, and ore material occurs as admixture or in layers.

Composition of Eocene claystones of ODP Hole 105-647A

Authigenic carbonates were recovered in lower to middle Eocene claystones at Ocean Drilling Program Site 647 in the Labrador Sea. Detailed chemical, petrographic, and X-ray investigations reveal that these diagenetic carbonates have a complex mineralogical composition. At least five different carbonate phases are identified: calcium-rich rhodochrosite, rhodochrosite, manganosiderite, siderite, and calcite. Manganese carbonates are the dominant carbonate phases formed throughout the section. Textural analyses show two major generations of carbonate formation. Early cementation of micritic carbonate in burrow structures was followed by carbonate cementation forming microsparry to sparry crystals. At approximately 620 meters below seafloor (mbsf), three concretions of iron carbonates occur, which indicates a special pore-water chemistry. Thin section analyses from this level show (1) several generations of diagenetic carbonates, (2) widespread secondary cavity formation in burrow structures, and (3) various cement precipitations in voids. We suggest that this level represents a hiatus or highly condensed sequence, as indicated by (1) the low carbonate content in host sediments, (2) carbonate dissolution reflected by the high ratio of benthic to planktonic foraminifers, and (3) complex diagenetic alteration in the carbonate concretions. Iron and manganese enrichments observed in lithologic Unit IV may have been derived from a hydrothermal source at the adjacent, then active, Labrador Sea mid-ocean ridge. Authigenic smectites forming numerous pseudomorphs of siliceous microfossils are precipitated in burrow structures. We propose that diagenetic smectite formation from biogenic opal and iron oxyhydroxide (analogous to smectite formation in surface sediments of the East Pacific area) occurred in the Labrador Sea during the early and middle Eocene.

Paleotemperature reconstructions on sediment core GIK161603-3

Different proxies for sea surface temperature (SST) often exhibit divergent trends for deglacial warming in tropical regions, hampering our understanding of the phase relationship between tropical SSTs and continental ice volume at glacial terminations. To reconcile divergent SST trends, we report reconstructions of two commonly used paleothermometers (the foraminifera G. ruber Mg/Ca and the alkenone unsaturation index) from a marine sediment core collected in the southwestern tropical Indian Ocean encompassing the last 37,000 years. Our results show that SSTs derived from the alkenone unsaturation index (UK'37) are consistently warmer than those derived from Mg/Ca by ~2-3°C except for the Heinrich Event 1. In addition, the initial timing for the deglacial warming of alkenone SST started at ~15.6 ka, which lags behind that of Mg/Ca temperatures by 2.5 kyr. We argue that the discrepancy between the two SST proxies reflects seasonal differences between summer and winter rather than post-depositional processes or sedimentary biases. The UK'37 SST record clearly mimics the deglacial SST trend recorded in the North Atlantic region for the earlier part of the termination, indicating the early deglacial warming trend attributed to local summer temperatures was likely mediated by changes in the Atlantic Meridional Overturning Circulation at the onset of the deglaciation, In contrast, the glacial to interglacial SST pattern recorded by G. ruber Mg/Ca probably reflects cold season SSTs. This indicates that the cold season SSTs was likely mediated by climate changes in the southern hemisphere, as it closely tracks the Antarctic timing of deglaciation. Therefore our study reveals that the tropical southwestern Indian Ocean seasonal SST was closely linked to climate changes occurring in both hemispheres. The austral summer and winter recorded by each proxy is further supported with seasonal SST trends modeled by AOGCMs for our core site. Our interpretation that the alkenone and Mg/Ca SSTs are seasonally biased may also explain similar proxy mismatches observed in other tropical regions at the onset of the last termination.

Graphene foam functionalized with electrodeposited nickel hydroxide for energy applications

The need of new systems for the storage and conversion of renewable energy sources is fueling the research in supercapacitors. In this work, we propose a low temperature route for the synthesis of electrodes for these supercapacitors: electrodeposition of a transition metal hydroxide–Ni(OH)2 on a graphene foam. This electrode combines the superior mechanical and electrical properties of graphene, the large specific surface area of the foam and the large pseudocapacitance of Ni(OH)2. We report a specific capacitance up to 900 F/g as well as specific power and energy comparable to active carbon electrodes. These electrodes are potential candidates for their use in energy applications.

Corrosión inducida por contaminantes hidrosolubles en la intercara metal/pintura

El objetivo principal de este trabajo es profundizar en el conocimiento del fenómeno de la corrosión subpelicular inducida por contaminantes hidrosolubles en la intercara metal/pintura. La contaminación salina del substrato es una situación común en la práctica: la superficie metálica suele estar expuesta a atmósferas contaminadas antes de ser recubierta, limpieza previa del metal con abrasivos contaminados, etc. La eliminación total de estos contaminantes resulta muy difícil de conseguir incluso con las técnicas más sofisticadas de limpieza. Esta investigación se centra en la determinación del efecto de la naturaleza del contaminante y la naturaleza y espesor del recubrimiento en el proceso de corrosión subpelicular del acero. En la investigación se utilizaron dos barnices de naturaleza diferente: poliuretano y vinílico; y se aplicaron a tres espesores diferentes. Los contaminantes empleados en este trabajo fueron: NaCl, NH4C1, CaCl2, Na2S04, (NH4)2S04, NaN03, NH4N03, Ca(N03)2. Los ensayos se realizaron en una cámara de condensación de humedad permanente. Los tiempos de exposición fueron 100, 300 y 600 horas. La velocidad de corrosión se evaluó gravimétricamente, mediante la técnica de pérdida de peso. Se realizaron estudios de permeabilidad al oxígeno y al agua de películas libres de substrato, evaluación de la velocidad de corrosión de probetas sin pintar inmersas en soluciones salinas de los contaminantes seleccionados, conductividad de dichas soluciones salinas, solubilidad del oxígeno en las soluciones salinas, adherencia en seco y en húmedo a diferentes tiempos de exposición. Se aporta evidencia respecto al control ejercido en el proceso corrosivo por el oxígeno que permea a través de la película, mientras que la permeación de agua controla la pérdida de adherencia del recubrimiento. Ambas permeabilidades dependen de la naturaleza del recubrimiento y de su espesor. Se ha investigado la influencia de la naturaleza del contaminante en la intercara metal/pintura. La naturaleza del catión parece quedar enmascarada por el efecto definitivo del anión. La concentración salina ejerce asimismo un efecto importante en la corrosión subpelicular. ABSTRACT The main aim of this work is to study in depth the knowledge of underfilm corrosión induced by hydrosoluble contaminants at the metal/paint Ínterface. The saline contamination of the substrate is a common situation in practice: metallic surfaces use to be exposed to polluted atmospheres, previous cleaning of the metal with contaminated abrasives, etc. Total elimination of these contaminants is hard to obtain even with modern cleaning techniques. This research is focused in determining the effect of contaminant nature, coating nature and its thickness on the steel underfilm corrosión process. In this work we used two varnishes with different nature: polyurethane and vinyl; they were applied in three different thicknesses. The saline contaminants employed were: NaCl, NH4C1, CaCl2, Na2S04, (NH4)2S04, NaN03, NH4N03/ Ca(N03)2. The tests were carried out in a condensation humidity chamber. The period of exposure were 100, 300 and 600 hours. Corrosión rate was assessed by weight loss. Simultaneously, studies on oxygen and water permeability of free films, assessing on corrosión rate of uncoated samples immersed in saline solutions of the selected contaminants, conductivity of these solutions, oxygen solubility in saline solutions, wet and dry adhesión of the polyurethane varnish at different periods of exposure, were carried out. There is clear evidence about control on corrosión process of oxygen that passes through the coating, while the passing of water controls the loss of adhesión of the coating. Both, water and oxygen permeation, depend on the nature and thickness of the coating. It has been researched the inf luence of the nature of contaminant at the metal/paint interface. The nature of the catión seems to be "masked" by the definitive effect of the nature of anión. The saline concentration also exerts an important effect on underfilm corrosión.

Dendritic cell modulation by 1α,25 dihydroxyvitamin D3 and its analogs: A vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo

Dendritic cells (DCs) play a central role in regulating immune activation and responses to self. DC maturation is central to the outcome of antigen presentation to T cells. Maturation of DCs is inhibited by physiological levels of 1α,25 dihydroxyvitamin D3 [1α,25(OH)2D3] and a related analog, 1α,25(OH)2-16-ene-23-yne-26,27-hexafluoro-19-nor-vitamin D3 (D3 analog). Conditioning of bone marrow cultures with 10−10 M D3 analog resulted in accumulation of immature DCs with reduced IL-12 secretion and without induction of transforming growth factor β1. These DCs retained an immature phenotype after withdrawal of D3 analog and exhibited blunted responses to maturing stimuli (CD40 ligation, macrophage products, or lipopolysaccharide). Resistance to maturation depended on the presence of the 1α,25(OH)2D3 receptor (VDR). In an in vivo model of DC-mediated antigen-specific sensitization, D3 analog-conditioned DCs failed to sensitize and, instead, promoted prolonged survival of subsequent skin grafts expressing the same antigen. To investigate the physiologic significance of 1α,25(OH)2D3/VDR-mediated modulation of DC maturity we analyzed DC populations from mice lacking VDR. Compared with wild-type animals, VDR-deficient mice had hypertrophy of subcutaneous lymph nodes and an increase in mature DCs in lymph nodes but not spleen. We conclude that 1α,25(OH)2D3/VDR mediates physiologically relevant inhibition of DC maturity that is resistant to maturational stimuli and modulates antigen-specific immune responses in vivo.